Lights, Camera, Immuno-action!

Melissa Bedard, a DPhil student in the Cerundolo Lab , writes about her research on invariant natural killer T cells, and the starring role they may be able to play in the fight against cancer.

We all know the classic plot line featured in countless spy and action movies. An intelligence team is defending a country against a foreign enemy or quelling an internal revolution. The team discovers that there is a traitor in their midst, trying to bring the team down from within – an individual who is not only hard to detect, but is also slowly converting others to their side. Only the protagonist can stop the bad guys. While we are familiar with this narrative on the silver screen, did you know that this could happen inside your body?

Allow me to set the stage: your body is equipped with a specialised system of cells to fight off harmful foreign agents – be it the virus that causes your cold, the bacteria that gives you food poisoning, or the fungus that causes your bout of Athlete’s Foot. This specialised system, the military of the body, is called the immune system, and the individual soldiers/spies are your immune cells. Just as the military has different divisions (navy, air force, etc.), so too does your immune system: T cells, dendritic cells, B cells, and neutrophils amongst others. Let’s focus on one of them: invariant natural killer T (iNKT) cells.

iNKT cells receive intel about the foreign agent by “reading” antigen, a little piece of the agent presented on the surface of infected cells, like a badge. Rather than directly eliminating the threat, they coordinate various other immune cells, each equipped with ‘a very particular set of skills’ (as said by Liam Neeson in Taken), to mount a broad, all-encompassing response against the threat. iNKT cells become naturally activated in certain types of cancer, but it is unclear how they become activated, given that there are often no foreign invaders involved in the disease. This is precisely the question I hope to answer in my research.

Now back to the screenplay: immune cells are going about their business, surveying the body for foreign invaders, when suddenly they sense something abnormal. However, it’s not a foreign invader like a virus or bacterium (cue a dramatic Hans Zimmer score), it’s something from your own body! This is what happens in cancer. Faulty cells multiply like crazy and disrupt surrounding cells, eventually harming the whole organ. For your immune system, it’s easy to detect foreign invaders, as they look very different from your own cells. However, in cancer, it is one of your own cells causing harm, and the soldiers of your immune system have been trained not to recognise and kill one of their own!

Your cells present little bits of themselves, called self-antigen, on their surface, which immune cells recognise to conclude that the cells are one of their own and thus should not be attacked. For this reason, even though these cancerous cells are causing harm, it is challenging for your immune cells to recognise them as harmful and mount a response. The cancerous cells that have converted to the ‘dark side’ can evolve to suppress and evade the immune system. How will the immune system defeat this internal threat?

Our lab is trying to better understand the ways in which immune cells recognise and fight cancer cells, and use this knowledge to manipulate immune cells to eliminate cancer — known as immunotherapy. While chemotherapy remains a frontline approach to treating cancer, it can have devastating effects on healthy parts of your body, making it difficult to tolerate. However, immunotherapy harvests the power of immune cells to specifically and efficiently target and kill cancer cells.

The research in our lab focuses on iNKT cells – we suspect that these cells are the protagonists who will save the day! iNKT cells recognise different types of antigens made from lipids (essentially a type of fat). We think that cancer cells, due to their abnormalities, present different types of self-lipid antigen – ones that activate iNKT cells and trigger an anti-tumour immune response. Specifically, my data suggests that cancer cells, which grow in a microenvironment lacking sufficient nutrients, oxygen etc., become stressed. Stress-response pathways in these cells are triggered, which alter lipid biosynthesis and lead to the presentation of activating self-lipid antigen to iNKT cells. An Oscar-worthy performance indeed! We hope to harness this process to develop vaccines against cancer. By exposing healthy people to these lipids through vaccination, the iNKT cells become ‘primed’ and ready to launch into action should a tumour start developing. Imagine a world in which cancer can be prevented!

While this plot line might sound exciting as a screenplay, in all seriousness, I’m sure all of us, either directly or indirectly, know someone who has received a cancer diagnosis. This personal connection drives our passion for our research and our hope that this work will contribute to improving cancer treatments and ultimately eliminating the disease.